MARIJUANA – THC and CBD – History, Metabolism

The active compound in marijuana, tetra hydro cannibal (THC), was first discovered in 1964 by an Israeli investigator. He felt it odd that morphine was discovered in opium in 1805 and cocaine from coca leaves in 1855, but that scientists had no idea what the principal psychoactive ingredient was in marijuana. Of the 10 compounds isolated from the plant, it was the only one that produced a “high”. The other active ingredient of most interest is cannibadiol (CBD), which has many potential medical uses (especially interesting is its effect in moderating electrical activity in the brain and its anti-seizure activity), but no psychoactive effect on humans.
There has only been one society on earth with no known “intoxicants”, the Inuit of the arctic simply because few plants grow there. One or two drugs are accepted and used in every society, each making its own choice. Marijuana use has been accepted by all societies but by few governments. A major attraction to marijuana is that overdose is unknown, and thus the general consensus is that it is “safe”. This is in contradistinction to pharmaceutical drugs that are responsible for fatal medical overdoses every 16 minutes.

DNA. The genome of marijuana is a relatively short sequence of 800 million nucleotides. A sketchy outline of the cannabis genome exists but is highly fragmented into 60,000 pieces. Once these fragments are assembled into the right order and the map is complete, it could be used to breed strains that contain much higher levels of one of the plant’s rare compounds with medically important properties. Besides understanding the biochemistry of the plant, insight will be gained into the human brain, neurology and psychology. Industry, agriculture, medicine and biofuels all have something to gain.

HEMP. Hemp produces fibres of unparalleled quality. It’s a tremendously high biomass crop that replenishes the soil and doesn’t require much in terms of inputs. It is illegal to grow in the US and tons are imported each year from China and Canada. It is a crop with huge profits. Now it is used to make CBD oil.

BRAIN RECEPTORS
Brain Function 101: Human gray matter contains around 86 billion neutrons that talk to each other through chemicals known as neurotransmitters – dopamine, serotonin, glutamate, and endocannabinoids – which in turn send instructions to your body about what to do. Endocannabinoids activate cannabinoid receptors in the brain. Only one plant produces a similar compound that hits those same receptors: marijuana. Just as poppy-derived morphine mimics endorphins, marijuana derived cannabinoids like THC and cannabidiol (CBD) mimic endocannabinoids. Cannabinoid receptors are especially widespread in the brain, where they play a key role in regulating the actions of other neurotransmitters. Practically every neurone either releases endocannabinoids or can sense them using cannabinoid receptors.
It was discovered that the receptors for THC in the brain resided in highest concentration in three parts of the brain: the hypocamus (memory), cerebellum (movement) and the frontal cortex (thinking). These different receptors regulate food intake and cravings and dopamine causing a sense of euphoria. It was reasoned that these receptors were not there to get high, but that there must be a “THC like” human molecule. In 1992, Mechoulam’s quest for quantification led him to isolate the chemical made by the human body that binds to the same receptor in the brain that THC does. He named it anandamide – from the Sanskrit for “supreme joy.” Since then several other enocannabinoids and their receptors have been discovered. Endocannabinoids interact with a specific neurological network – much the same way that endorphins, serotonin, and dopamine do. They apparently play an important role in such basic functions as pain, mood, appetite, memory, balance, movement, immune health, and neuroprotection. Marijuana contains numerous substances – cannabinoids, flavonoids, terpenes – that have never been investigated in depth. The low-THC strains are particularly high in these compounds. Encannabinnoids also play a life and death role of individual cells. Interestingly, cannabinoid receptors aren’t densely packed in the medulla in the brain stem that controls breathing and the cardiovascular system. That’s why a heroin overdose generally can be fatal (the drug shuts down the respiratory control centre), but a marijuana overdose can’t.
Pharmaceutical companies making cannabis-based medicines have sought to isolate individual compounds from the plant. But it is suspected that those compounds work much better in concert with other compounds found in marijuana. It may well be discovered that cannabinoids are involved in some way in all human diseases. Only the surface has been scratched.
Endocannabinoids have all the same properties of THC and affect appetite, pain and memory. Why would there be a natural substance that affects memory? What adaptive function could that have? When thought about, it becomes obvious that you do not want to remember everything – there are hundreds of things we encounter every day that are irrelevant and would overload our brains if remembered. Forgetting may be just as important as remembering. It has an editing function.
Neurotransmitters carry out brain communication through synapses, but too much synaptic excitation is poisonous and damages cells. Endocannabinoids are a mechanism for putting on the brakes when that toxic level of excitation is approached. Cannabinoids like CBD may be thought of as neuroprotectants, The US National Institutes of Health actually owns a patent on cannabinoids as neuroprotectants. This was based on research that showed CBD showed particular promise intimating neurological damage in patients wit Alzheimer’s disease and Parkinson’s disease, and in those who have suffered a stroke or head trauma.
Its use in PTSD owes its role in extinguishing unpleasant memories. Part of PTSD is due to the brains’s stress buffers being blown out by trauma. Endocabinnoids in the amygdala (the brain region important for emotional learning and memory) act as a key mechanism for memory extinction.

METABOLISM
When you smoke pot, the psychoactive ingredient, THC, spreads throughout your body but leaves your body quickly as it is absorbed by your fatty tissues and brain, so that the amount of THC in the blood is not a good indicator of impairment. It is even possible to have less THC in your blood when the effects of pot are at their peak, usually about 10-30 minutes after your last puff.
The first receptors stimulated by THC induce pleasure, with impaired coordination and increased appetite – a good-all-over feeling. Most become more creative due to a drug-induced release of dopamine which causes one to see things differently and decrease inhibition.
Because of its long half-life and high lipid solubility, it has been shown that using marijuana more than twice per week results in accumulation of the drug. It is stored in all lipid tissues but especially in the myelin sheaths of nerves, the high fat content “insulation” that surrounds all nerves. Large globules of THC can be seen under magnification in the myelin. it is one of the reasons why withdrawal and craving are uncommon (especially in the90% of users who are not dependent) when stopping marijuana use. Indeed, if the drug was not around, most habitual users never think about it. It is unlikely that craving ever occurs when all drug is eventually gone as withdrawal is so slow.

EVOLUTIONARY IMPORTANCE
It is also thought that anandamide has significant evolutionary importance. When hunting, it is often necessary to be silent for long periods of time, for example when sitting in a blind waiting for that deer to walk by. There would be value in forgetting (that you had just sat there for 4 hours), concentration (focusing on just one thing), and appetite (what better drive could there be when hunting). This is thought to be a new physiologic system of immense importance.Running triggers the release of endocannabinoids (anandamide) that create a potent feeling of pleasure and are a main cause of “runners high”. From an evolutionary standpoint this makes sense. Remaining fit enough to run after game and away from predators and enemies was vital for survival. Other animals that gain an evolutionary benefit from being fast on their feet (antelopes, horses, and wolves for example), have a greater response to cannabinoids, and thus experience a runners high, than animals that are known for being quick and aggressive (ferrets). The latter do not reward cardiovascular activity, since such exercise consume a lot of energy, may cause injury and is not crucial to the stealthy hunting technique.

HISTORY OF USE
In Siberia charred seeds have been found inside burial mounds dating back to 3000 BC. The Chinese were using cannabis as medicine thousands of years ago. It spread out from Central Asia after the last ice age and went out across the planet with man. Humans evolved with marijuana practically since the dawn of time. It’s older than writing and has always been part of us. George Washington grew hemp at Mount Vernon. For most of US history, cannabis was legal, commonly found in tinctures and extracts.
With the production of the documentary “Reefer Madness” in 1930, it became public enemy #1. Declared illegal in 1937 in the US, the plant went into hiding and medical research largely stopped. The federal government made it even harder to study marijuana in 1970 when it was made a Schedule I controlled drug with no medical value and a high potential for abuse, in the same category as heroin. When marijuana use became popular in the 1970s, governments felt that they had to take action. In the United States, the National Institute of Drug Abuse (NIDA) blocks all marijuana research by producing many bureaucratic loops to getting approval. Only 6% of studies done in the US look for the good effects and the rest for the harm. It is a strange kind of scientific trade deficit. The US leads the world in studies of marijuana’s harm but is also a net importer of data dealing with its healing potential.
Initially most of the drug came from Mexico, but when the US government became involved in spraying paraquat on Mexican fields, smokers became worried about exposure to the herbicide. This encouraged domestic cultivation especially in California. When the government started to spray paraquat on this, it moved indoors. However the native strain, cannabis sativa was tall and sparse and not well suited to indoor growth. It was then crossed with another strain, cannabis indica that was a fast, short, strong, hardy, mountain strain. Hybridization is continuous always selecting for qualities that are most desirable.
Now, as medical uses are becoming more known, the science of marijuana is experiencing a rebirth.
In the late 1990s, both the US and British governments commissioned separate studies on medical marijuana. And both produced similar conclusions: that medial pot held real therapeutic potential for specific conditions. The British responded by licensing GW Pharmaceuticals to develop cannabinoid drugs. But America instead doubled down on the war on drugs claiming the opposite of the report’s conclusions. Tougher strictures on the study of marijuana as a medicine were instituted.
In 2015, the Colorado department of public health awarded $9 million in grants for medical-marijuana research, funded with tax revenue from state-licensed pot stores. They will be the first US clinical studies to look into the effectiveness of marijuana for childhood epilepsy, irritable-bowel disease, cancer pain, PTSD and Parkinson’s disease.

THE WAR ON DRUGS
In the USA, there are 750,000 arrests for marijuana possession, cultivation and trafficking every year. It represents one third of all crimes and 30-50,000 people are in jail at any one time related to the drug. It is classed as Schedule I narcotic in the same class as heroin. Cocaine and morphine are Schedule II drugs and attract research. That also means that under the law, marijuana has “no medical benefit”, even though 23 states have legalized pot as medicine. Marijuana researchers face barriers even higher than those faced by scientists studying other Schedule I drugs (heroin, LSD) as pot studies must pass intensive review by the US Public Health Service, a process that has delayed and thwarted much research for more than 15 years. The government’s research restrictions are so severe that it’s difficult to find and show the medical benefit. A bill was introduced in March 2015 to federally legalize medical marijuana in states that have already approved it. The American prison system is overloaded with marijuana related inmates and the cost of their care is bankrupting the system.
Unfortunately Canada has followed in the footsteps of the US, at least partly because of intense pressure from the US government. Our conservative government is devoting huge energy in prosecuting growers and minor possession. Just like the US, these laws will clog our court system, jails and only increase cost. There are many reasons for legalizing marijuana. Revenue from taxation could be considerable. It takes the major player in illegal drug distribution, the Hells Angels out of the system. The cost of incarceration far outstrips the cost of drug treatment and jails hardly seem like the best place for use of a relatively innocuous drug.
The “War on Drugs” has been a huge failure in the US. It is a campaign of prohibition and foreign military undertaken by the US government, with the assistance of participating countries, with the stated aim to define and reduce the illegal drug trade. In 1937, the Marijuana Transfer Tax Act had the goal to destroy the hemp industry, and was largely the effort of Andrew Mellon, Randolf Hearst, and the DuPont family. Hemp was seen as a substitute for paper pulp and was a threat to the men’s timber holdings and to the new synthetic fiber nylon.

ISRAEL
Israel is the only country in the world actively involved in research into marijuana. An Israeli, Raphael Mechoulam isolated THC and CBD in 1963. Mechoulam is widely known as the patriarch of cannabis science. He’s a respected member of the Israel Academy of Sciences and Humanities and an emeritus professor at Hebrew University’s Hadassah Medical School, where he still runs a lab. The author of more than 400 scientific papers and the holder offbeat 25 patents, he has spent a lifetime studying cannabis, which he calls a “medicinal treasure trove waiting to be discovered.” His work has spawned a subculture of cannabis research around the globe. Though he says he’s never smoked the stuff, he’s a celebrity in the pot world.
Israel has one of the world’s most advanced medical marijuana programs. Mechoulam played an active role in setting it up, and he’s proud of the results. More than 20,000 people in Israel are on medical marijuana for glaucoma, Crohn’s disease, inflammation, pain, loss of appetite, Parkinsons disease, dementia, hand tremors, nightmares (especially useful in holocaust survivors and PTSD), Tourette’s Syndrome and asthma.
Despite that, he’s not particularly in favour of legalizing cannabis for recreational use. He doesn’t think anyone should go to jail for possessing it, but he insists that marijuana is not an innocuous substance – especially for young people. Many studies show that the prolonged use of high-THC stains of marijuana can change the way the developing brain grows. In some people cannabis can provoke serious and debilitating anxiety attacks.
He desires an earnest and enthusiastic embrace of cannabis – but only as a medical substance to be strictly regulated and relentlessly researched. For it to work in the medical world, it has to be quantitative, If you can’t count it, it’s not science.

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I would like to think of myself as a full time traveler. I have been retired since 2006 and in that time have traveled every winter for four to seven months. The months that I am "home", are often also spent on the road, hiking or kayaking.
I hope to present a website that describes my travel along with my hiking and sea kayaking experiences.